Primary amines reductive amination

The azo-compounds are usually very stable, and can be directly chlorinated, nitrated and sulphonated. On vigorous reduction the molecule splits at the azo group to give two molecules of primary amines, e.g. bcnzene-azophenol gives PhNH2 and p-HOC H NHa. 

The most noteworthy reaction of azo-compounds is their behaviour on reduction. Prolonged reduction first saturates the azo group, giving the hydrazo derivative (C NH-NH C), and then breaks the NH NH linkage, with the formation of two primary amine molecules. If method (1) has been employed to prepare the azo-compound, these two primary amines will therefore be respectively (a) the original amine from which the diazonium salt was prepared, and (6) the amino derivative of the amine or phenol with which the diazonium salt was coupled. For example, amino-azobenzene on complete reduction gives one equivalent of aniline, and one of p-phenylene diamine, NHaCeH NH benzene-azo-2-naphthoI similarly gives one equivalent of aniline and one of... 

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

Reduction of a nitro compound to a primary amine. In a 50 ml. round-bottomed or conical flask fitted with a reflux condenser, place 1 g. of the nitro compound and 2 g. of granulated tin. Measure out 10 ml. of concentrated hydrochloric acid and add it in three equal portions to the mixtiue shake thoroughly after each addition. When the vigorous reaction subsides, heat under reflux on a water bath until the nitro compound has completely reacted (20-30 minutes). Shake the reaction mixture from time to time if the nitro compound appears to be very insoluble, add 5 ml. of alcohol. Cool the reaction mixture, and add 20-40 per cent, sodium hydroxide solution imtil the precipitate of tin hydroxide dissolves. Extract the resulting amine from the cooled solution with ether, and remove the ether by distillation. Examine the residue with regard to its solubility in 5 per cent, hydrochloric acid and its reaction with acetyl chloride or benzene-sulphonyl chloride. 

Nitro groups are readily reduced to primary amines by a variety of methods Cat alytic hydrogenation over platinum palladium or nickel is often used as is reduction by iron or tin m hydrochloric acid The ease with which nitro groups are reduced is especially useful m the preparation of arylamines where the sequence ArH ArN02 ArNH2 IS the standard route to these compounds... 

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

Controlled-potential coulometry also can be applied to the quantitative analysis of organic compounds, although the number of applications is significantly less than that for inorganic analytes. One example is the six-electron reduction of a nitro group, -NO2, to a primary amine, -NH2, at a mercury electrode. Solutions of picric acid, for instance, can be analyzed by reducing to triaminophenol. 

Analogously, aldehydes react with ammonia [7664-41-7] or primary amines to form Schiff bases. Subsequent reduction produces a new amine. The addition of hydrogen cyanide [74-90-8] sodium bisulfite [7631-90-5] amines, alcohols, or thiols to the carbonyl group usually requires the presence of a catalyst to assist in reaching the desired equilibrium product. 

Industrially, polyurethane flexible foam manufacturers combine a version of the carbamate-forming reaction and the amine—isocyanate reaction to provide both density reduction and elastic modulus increases. The overall scheme involves the reaction of one mole of water with one mole of isocyanate to produce a carbamic acid intermediate. The carbamic acid intermediate spontaneously loses carbon dioxide to yield a primary amine which reacts with a second mole of isocyanate to yield a substituted urea. 

Reductive amination of cyclohexanone using primary and secondary aHphatic amines provides A/-alkylated cyclohexylamines. Dehydration to imine for the primary amines, to endocycHc enamine for the secondary amines is usually performed in situ prior to hydrogenation in batch processing. Alternatively, reduction of the /V-a1ky1ani1ines may be performed, as for /V,/V-dimethy1 cyclohexyl amine from /V, /V- di m e th y1 a n i1 i n e [121 -69-7] (12,13). One-step routes from phenol and the alkylamine (14) have also been practiced. 

Morpholiaoglucopyranosides have beea syathesized from sucrose by selective lead tetraacetate oxidatioa of the fmctofuranosyl ring to a dialdehyde (6). This product was subjected to reductive amination with sodium borohydride and a primary amine such as benzylamine to produce the /V-henzy1morpho1ino derivative (7) (99). 

Catalytic hydrogenation of the nitrile function of cyanohydrins can give amines. As in the case of ordinary nitriles, catalytic reduction of cyanohydrins can yield a mixture of primary, secondary, and tertiary amines. Addition of acid or acetic anhydride to the reaction medium minimizes formation of secondary or tertiary amines through formation of the amine salt or acetamide derivative of the primary amine. 

FORSTER - DECKER Amine Synthesis Selective monoalkylation of primary amines via imines An altemativa method is the reaction ol 1 and 2 in the preserve of NaCNBH4 or tnaceloxyborohydride (Borch reduction)/... 

The common impurities found in amines are nitro compounds (if prepared by reduction), the corresponding halides (if prepared from them) and the corresponding carbamate salts. Amines are dissolved in aqueous acid, the pH of the solution being at least three units below the pKg value of the base to ensure almost complete formation of the cation. They are extracted with diethyl ether to remove neutral impurities and to decompose the carbamate salts. The solution is then made strongly alkaline and the amines that separate are extracted into a suitable solvent (ether or toluene) or steam distilled. The latter process removes coloured impurities. Note that chloroform cannot be used as a solvent for primary amines because, in the presence of alkali, poisonous carbylamines (isocyanides) are formed. However, chloroform is a useful solvent for the extraction of heterocyclic bases. In this case it has the added advantage that while the extract is being freed from the chloroform most of the moisture is removed with the solvent. 

Reduction of nitriles (Section 22.9) Nitriles are reduced to primary amines by lithium aluminum hydride or by catalytic hydrogenation. 

The use of primary amines instead of ammonia affords l,2-dialkyl-/l -pyrrolines or l,2-dialkyl-/l -piperideines. Amino ketones with a primary amino group are intermediates in the reduction of y-nitropropylalkyl ketones (14,15) or S-nitrobutylalkyl ketones (16-18) by catalytic hydrogenation over Raney nickel or with zinc and hydrochloric acid (Scheme 1). 

Aniline 77 was converted into its diazonium salt with nitrous acid and this was followed by reduction with stannous chloride to afford the corresponding arylhydrazine 78. Condensation of 78 with 3-cyanopropanal dimethylacetal 79 gave the arylhydrazone 80. Treatment of 80 with PPE resulted in cyclization to indole 81. The nitrile group was then reduced to the primary amine by catalytic hydrogenation. Reaction of the amine with excess formalin and sodium borohydride resulted in Imitrex (82). 

Reduction of phenylacetone in the presence of methylamine rather than ammonia gives methamphetamine (53), an agent similar in action to the primary amine. Alkylation of 53 with benzyl chloride affords the analog, benzphetamine (54). ... 

Preparation of the key tropine is achieved by any one of several variations on the method first developed by Robinson, which involves reaction of a primary amine with dihydroxyacetone and glyoxal. Reduction of the carbonyl group in the product (86) followed by acylation affords the aminoester (88). Transesterification with ester aldehyde 89... 

---